How it all starts: Initiation of the clotting cascade
Open accessAbstract
The plasma coagulation system in mammalian blood consists of a cascade of enzyme activation events in which serine proteases activate the proteins (proenzymes and procofactors) in the next step of the cascade via limited proteolysis. The ultimate outcome is the polymerization of fibrin and the activation of platelets, leading to a blood clot. This process is protective, as it prevents excessive blood loss following injury (normal hemostasis). Unfortunately, the blood clotting system can also lead to unwanted blood clots inside blood vessels (pathologic thrombosis), which is a leading cause of disability and death in the developed world. There are two main mechanisms for triggering the blood clotting, termed the tissue factor pathway and the contact pathway. Only one of these pathways (the tissue factor pathway) functions in normal hemostasis. Both pathways, however, are thought to contribute to thrombosis. An emerging concept is that the contact pathway functions in host pathogen defenses. This review focuses on how the initiation phase of the blood clotting cascade is regulated in both pathways, with a discussion of the contributions of these pathways to hemostasis versus thrombosis.
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Hemostasis is achieved within the first minutes to hours of injury through a series of serine protease events designed to prevent blood loss.
“The initial events following injury are designed to achieve hemostasis within the first minutes to hours of injury based on a series of serine protease events designed to prevent blood loss [11].”
From Immunology of Wound Healing (2018) · cites this paper as [11]
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- Renné T Marder VJ Aird WC Bennett JS Schulman S White GC 2nd The factor XII-driven plasma contact system Hemostasis and Thrombosis: Basic Principles and Clinical Practice 2013 6th Philadelphia Lippincott Williams & Wilkins
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Emerging materials for hemostasis
Li, X.-F., Lu, P., Jia, H.-R., Li, G., Zhu, B., Wang, X., & Wu, F.-G. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2022.214823 · Cited by 164 · see citing works
Using machine learning to identify clotted specimens in coagulation testing
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Gluing blood into gel by electrostatic interaction using a water-soluble polymer as an embolic agent
Jin, Z., Fan, H., Osanai, T., Nonoyama, T., Kurokawa, T., Hyodoh, H., Matoba, K., Takeuchi, A., Gong, J. P., & Fujimura, M. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2206685119 · Cited by 16 · see citing works
- Authors
- Smith, S. A., Travers, R. J., & Morrissey, J. H.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Morrissey, James H.
- Venue
- Critical Reviews in Biochemistry and Molecular Biology
- Publisher
- Informa UK Limited
- Published
- 2015-05-28
- Volume
- 50
- Issue
- 4
- Pages
- 326-336
- ISSN
- 0045-6411 (ISSN-L)
- 1040-9238
- 1549-7798
- PMC
- PMC4826570
- OpenAlex
- W1817123886
- Cited by
- 529
- References
- 176
- Citations by year
- 2026: 32 · 2025: 60 · 2024: 92 · 2023: 72 · 2022: 77 · 2021: 64 · 2020: 50 · 2019: 34 · 2018: 28 · 2017: 7 · 2016: 9 · 2015: 3 · 2014: 1
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Critical Reviews in Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL103999, R01HL047014)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Keywords
- coagulation, extrinsic coagulation pathway, contact pathway, serine protease, limited proteolysis, fibrin polymerization, platelet activation, hemostasis, thrombosis
- MeSH terms
- Animals, Blood Coagulation, Hemostasis, Humans, Models, Biological, Thromboplastin, Thrombosis, Platelet Activation, Proteolysis
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